Human alpha-thrombin is being produced in gram quantities for detailed studies on the protein structure, enzymic specificity, and biologic functions of this central bioregulatory serine protease in hemostasis. In addition to this procoagulant form, noncoagulant Beta-and gamma-thrombins and other forms are being made for investigating extended active-site regions involved in protein binding or recognition. Current studies include: direct activation of prothrombin to noncoagulant thrombins, improved isolation methods for these forms, selective chemical modification of thrombin active-site regions, and the assessment active-site regions defining proteolytic specificity. Related collaborative studies are directed at determining how alpha-thrombin interacts not only with fibrinogen but also with cellular receptors. Data from our and collaborative studies strongly that alpha-thrombin has unique protein-binding or recognition sites, which are independent of its catalytic site, and can account for its physiological specificity.